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Real-world data in patients with moderate psoriasis treated with apremilast is limited.To evaluate the effectiveness and safety of apremilast in bio-naïve patients with moderate psoriasis in real-world clinical settings.This was a 52-week multicenter, observational, prospective study of adult outpatients with moderate psoriasis {[10% body surface area 20% or 10 psoriasis area severity index (PASI) 20] and 10 dermatology quality of life index (DLQI) 20} initiated on apremilast ≤7 days before enrollment. Missing data were imputed using the last observation carried forward method.A total of 287 eligible patients (median age: 54.2 years; median psoriasis duration: 9.8 years) were consecutively enrolled. At baseline, the median DLQI and PASI scores were 12.0 and 11.8, respectively. The 52-week DLQI ≤ 5 and PASI75 response rates were 68.3% and 61.0%. At 52 weeks, 70.8% and 72.7% of the patients shifted from moderate/severe/very severe to clear/minimal scalp and palmoplantar psoriasis involvement, respectively; the pruritus severity state improved in 67.2%. The 52-week Kaplan-Meier estimated drug continuation rate was 85.3%. The adverse drug reaction rate was 19.9%.Apremilast is a safe and effective treatment for bio-naïve patients with moderate psoriasis and specific psoriasis manifestations.

Summary Background. Local complications of erysipelas include haemorrhagic, bullous, abscessing and necrotic lesions. The risk factors predisposing patients to local complications are not fully known. Aim. To examine local complications of erysipelas and to identify possible risk factors predisposing to their appearance. Methods. Medical records from all patients hospitalized with complications of erysipelas (purpura, bullae, abscesses and necrosis), admitted to the University Hospital of Heraklion between 1994 and 2002, were retrospectively studied. Clinical and laboratory data were compared with those from patients with erysipelas without local complications. Results. In total, 145 patients were analysed, of whom 46 had local disease complications. Using bivariate analysis, the factors significantly associated with disease complications were found to be age ≥ 51 years, obesity, longer duration of local symptoms, and fever on admission. During hospitalization, increased C-reactive protein level, isolation of pathogens, longer duration of fever and/or presence of leucocytosis, absence of response to initial antibiotic therapy, and longer length of hospitalization were also associated with complications in the bivariate analysis. However, in the multivariate analysis, obesity (OR 4.489, 95% CI 1.719–11.725, P = 0.002) was the only independent factor associated with complicated erysipelas. Conclusions. This study found obesity to be an independent risk factor for local complications, of erysipelas. Hence, obese patients with erysipelas are prone to complications, and should be carefully evaluated because of the potential severity of disease and the increased risk of failure of empirical antimicrobial therapy.

Transforming growth factor-β is a potent growth inhibitor for normal melanocytes. This function is lost in the course of tumorigenesis, since several melanoma cell lines are only slightly or not at all inhibited by TGF-β. In melanoma, the transduction of antiproliferative signals by TGF-β is often abolished, and the autocrine production of TGF-β increased. By this way, several TGF-β-driven paracrine effects, such as extracellular matrix remodeling, neoangiogenesis, and immunosuppression induce local tumor growth and metastasis. The interaction of Smads, the major TGF-β signaling proteins, with other signaling systems such as the mitogen-activated protein kinases, the SKI/SnoN proteins, and the protein kinase C family, possibly contributes to the escape of melanoma cells from TGF-β growth control. Therefore, the clarification of the molecular interactions of the TGF-β signaling pathway may further promote the development of new treatment concepts for melanoma.

Basic fibroblast growth factor (FGF-2) and its respective tyrosine kinase receptors, form an autocrine loop that affects human melanoma growth and metastasis. The aim of the present study was to examine the possible participation of various glycosaminoglycans, i.e. chondroitin sulfate, dermatan sulfate and heparin on basal and FGF-2-induced growth of WM9 and M5 human metastatic melanoma cells. Exogenous glycosaminoglycans mildly inhibited WM9 cell's proliferation, which was abolished by FGF-2. Treatment with the specific inhibitor of the glycosaminoglycan sulfation, sodium chlorate, demonstrated that endogenous glycosaminoglycan/proteoglycan production is required for both basal and stimulated by FGF-2 proliferation of these cells. Heparin capably restored their growth, and unexpectedly exogenous chondroitin sulfate to WM9 and both chondroitin sulfate and dermatan sulfate to M5 cells allowed FGF-2 mitogenic stimulation. Furthermore, in WM9 cells the degradation of membrane-bound chondroitin/dermatan sulfate stimulates basal growth and even enhances FGF-2 stimulation. The specific tyrosine kinase inhibitor, genistein completely blocked the effects of FGF-2 and glycosaminoglycans on melanoma proliferation whereas the use of the neutralizing antibody for FGF-2 showed that the mitogenic effect of chondroitin sulfate involves the interaction of FGF-2 with its receptors. Both the amounts of chondroitin/dermatan/heparan sulfate and their sulfation levels differed between the cell lines and were distinctly modulated by FGF-2. In this study, we show that chondroitin/dermatan sulfate-containing proteoglycans, likely in cooperation with heparan sulfate, participate in metastatic melanoma cell FGF-2-induced mitogenic response, which represents a novel finding and establishes the central role of sulfated glycosaminoglycans on melanoma growth.

Summary We report a case of cutaneous alternariosis in a 69-year-old male patient. During hospitalization for treatment of the skin disorder, acute myeloid leukaemia was diagnosed. He received multiple chemotherapeutic agents but the leukaemia remained refractory to therapy and the patient died. The clinical picture, diagnosis and treatment of cutaneous alternariosis will be discussed and a review of the literature regarding patients with haematological diseases will be given. Zusammenfassung Wir berichten ubet einen Fall einer kutanen Alternariose bei einem 69-jahrigen mannlichen Patienten. Wahrend seines stationaren Aufenthaltes zur Behandlung seiner Hauterkrankung, wurde eine akute myeloische Leukamie diagnostiziert. Er erhielt Polychemotherapie, aber die Leukamie blieb therapierefraktar, und der Patient verstarb. Das klinische Bild, die Diagnose und die Behandlung der kutanen Alternariose wird besprochen und ein Review der Literatur wird beigefugt uber Alternariosen bei hamatologischen Erkrankungen.

Engagement of integrin receptors during cell adhesion leads to changes in the morphology and the state of activation of cells. We therefore examined whether mast cell adhesion to extracellular matrix proteins affects the synthesis and release of various proinflammatory cytokines. Cells of the human mast cell line HMC-1 were added to fibronectin (FN)-, vitronectin (VN)- or, as a control, bovine serum albumin (BSA)-coated wells and were stimulated with phorbol 12-myristate 13-acetate (PMA) and/or calcium ionophore A23187 (ionophore). Cytokine production was evaluated using semiquantitative reverse transcription–polymerase chain reaction (RT–PCR) analysis of cell extracts and enzyme-linked immunosorbent assay (ELISA) analysis of cell supernatants. After a 4-hr incubation, mRNA expression of interleukin (IL)-8 (and weakly of IL-6) was up-regulated in matrix-adherent cells, with further increase in the presence of PMA and/or ionophore, compared with unstimulated cells. High-level de novo expression of IL-3 and of granulocyte–macrophage colony-stimulating factor (GM-CSF) was observed mainly in matrix-adherent cells. These changes were paralleled by the secretory pattern of HMC-1 cells after a 24-hr stimulation. Unstimulated cells adherent to FN or VN had already released small amounts of IL-8, and both VN- and FN-adherent cells produced, almost invariably, a higher level of cytokines than BSA-exposed cells after additional stimulation. These results show that mast cell adhesion to matrix proteins by itself has only selected and minor effects, but additional activation of mast cells by secretory stimuli causes significantly enhanced cytokine gene expression and secretion, suggesting that mast cells are far more active in their natural tissue environment than hitherto suggested from data in suspension cultures.

We studied, in vitro, the stimulating effects of a commercial preparation of low molecular thymic peptides (TP) on the immunocytotoxicity of peripheral blood lymphocytes and monocytes from patients with breast tumors, melanoma and colorectal tumors. On average, tumor patients showed a lower natural killer (NK), lymphokine (IL-2) activated killer (LAK) cell and basic tumoristatic activity of monocytes, compared with healthy donors. There was no correlation between the NK-cell number and the NK-cell activity of the tumor patients. The TP showed no effects on the NK-cell activity in any group, yet elevated the deficient LAK-cell activity of tumor patients and that of healthy donors. On monocytes, TP enhanced the deranged tumoristatic activity only in tumor patients, while being slightly inhibitory on control monocytes. Dividing the donors on the basis of the TP effects on cytotoxicity of the mononuclear cells into TP-nonresponders and TP-responders, a higher number of TP-responders was found among tumor patients, compared with healthy donors. Moreover, a higher number of TP-nonresponders were observed with lymphocytes from colorectal tumor patients at advanced tumor stage. Therefore, on the basis of the applied immunocytotoxic assays, these results may provide a basis for selecting tumor patients, who may respond to TP in immunotherapy protocols.

The effects of a thymic peptide preparation (TP) on the immunocytotoxicity and cytokine secretion of peripheral blood lymphocytes and monocytes from patients with colorectal tumors, breast tumors and melanoma were studied in vitro. On average, breast tumor and melanoma patients showed significantly lower natural killer (NK) cell activities than colorectal tumor patients and normal controls. In contrast, the generation of lymphokine (IL-2) activated killer (LAK) cells was found to be comparable within the different tumor diseases (24% cytotoxicity), but lower than in the group of normal controls. TP, being without any effects on NK cell activity in all groups, increased the deficient LAK cell activity of breast tumor and melanoma patients, as well as of normal controls? without significant effects on PBL from colorectal tumor patients. This increase was found to be associated with an increase of the IL-2 induced IFN-gamma and, on a lower level, TNF-alpha secretion, especially from breast tumor and melanoma patients. In addition, monocytes from these patients showed a deranged tumoristatic activity, compared to colorectal tumor patients and normal controls. The stimulation of monocytes by IFN-gamma greatly elevated the mean of the antitumor activity in all groups studied. TP being slightly effective on monocytes from melanoma patients, did not further enhance monocyte-mediated cytotoxicity when applied alone or in combination with IFN-gamma. Reduced basal monocytic chemokine levels were only found in the groups of melanoma (IL-8) and colorectal tumor patients (MCP-1), whereas RANTES secretion was increased, compared to normal controls. TP was active only in reducing the IL-8 secretion of monocytes from colon tumor patients. The results indicate that selected functions of peripheral blood mononuclear cells can be partially improved by the thymic peptide preparation.

Local complications of erysipelas include haemorrhagic, bullous, abscessing and necrotic lesions. The risk factors predisposing patients to local complications are not fully known.To examine local complications of erysipelas and to identify possible risk factors predisposing to their appearance.Medical records from all patients hospitalized with complications of erysipelas (purpura, bullae, abscesses and necrosis), admitted to the University Hospital of Heraklion between 1994 and 2002, were retrospectively studied. Clinical and laboratory data were compared with those from patients with erysipelas without local complications.In total, 145 patients were analysed, of whom 46 had local disease complications. Using bivariate analysis, the factors significantly associated with disease complications were found to be age ≥ 51 years, obesity, longer duration of local symptoms, and fever on admission. During hospitalization, increased C-reactive protein level, isolation of pathogens, longer duration of fever and/or presence of leucocytosis, absence of response to initial antibiotic therapy, and longer length of hospitalization were also associated with complications in the bivariate analysis. However, in the multivariate analysis, obesity (OR 4.489, 95% CI 1.719-11.725, P = 0.002) was the only independent factor associated with complicated erysipelas.This study found obesity to be an independent risk factor for local complications, of erysipelas. Hence, obese patients with erysipelas are prone to complications, and should be carefully evaluated because of the potential severity of disease and the increased risk of failure of empirical antimicrobial therapy.

Melanoma is a frequent and therapy-resistant human disease. Malignant melanocytes modulate their microenvironment in order to penetrate the dermal/epidermal junction and eventually invade the dermis. The small leucine-rich proteoglycans (SLRPs) constitute important constituents of the dermis extracellular matrix (ECM), participating in both the structural and the functional organization of the skin. The role of a keratan sulphate SLRP lumican, has recently been investigated in the growth and metastasis of several cancers. In this study, the expression of lumican was studied in two human melanoma cell lines (WM9, M5) as well as in normal neonatal human melanocytes (HEMN) using real time PCR, western blotting with antibodies against the protein core and keratan sulfate, and treatments with specific enzymes. Both human metastatic melanoma cell lines were found to express lumican mRNA and effectively secrete lumican in a proteoglycan form, characterized to be substituted mostly with keratan sulfate chains. Lumican mRNA was not detected in normal melanocytes. This is the first time that the synthesis and secretion of lumican in human melanoma cell lines is reported. The role of this proteoglycan in the development and progression of malignant melanoma has to be further investigated.

We report a case of cutaneous alternariosis in a 69-year-old male patient. During hospitalization for treatment of the skin disorder, acute myeloid leukaemia was diagnosed. He received multiple chemotherapeutic agents but the leukaemia remained refractory to therapy and the patient died. The clinical picture, diagnosis and treatment of cutaneous alternariosis will be discussed and a review of the literature regarding patients with haematological diseases will be given.

Die jungsten Entwicklungen zur Pathogenese des Merkelzellkarzinoms haben unser Verstandnis fur diesen Tumor betrachtlich verbessert. Die klonale Integration des Merkelzell(polyom)virus ins Genom der Tumorzellen und die tumorspezifische verkurzende Mutation des LT-Antigens wahrend der Integration ist dabei der wesentliche Mechanismus, der zur Entartung der Zellen fuhrt. Weitere Ereignisse tragen offensichtlich zur Merkelzelltransformation bei, wie die simultane Expression des Stammzellfaktors und seines Rezeptors KIT, was eine autokrine Forderung des Zellwachstums bewirkt.

Engagement of integrin receptors during cell adhesion leads to changes in the morphology and the state of activation of cells. We therefore examined whether mast cell adhesion to extracellular matrix proteins affects the synthesis and release of various proinflammatory cytokines. Cells of the human mast cell line HMC-1 were added to fibronectin (FN)-, vitronectin (VN)- or, as a control, bovine serum albumin (BSA)-coated wells and were stimulated with phorbol 12-myristate 13-acetate (PMA) and/or calcium ionophore A23187 (ionophore). Cytokine production was evaluated using semiquantitative reverse transcription–polymerase chain reaction (RT–PCR) analysis of cell extracts and enzyme-linked immunosorbent assay (ELISA) analysis of cell supernatants. After a 4-hr incubation, mRNA expression of interleukin (IL)-8 (and weakly of IL-6) was up-regulated in matrix-adherent cells, with further increase in the presence of PMA and/or ionophore, compared with unstimulated cells. High-level de novo expression of IL-3 and of granulocyte–macrophage colony-stimulating factor (GM-CSF) was observed mainly in matrix-adherent cells. These changes were paralleled by the secretory pattern of HMC-1 cells after a 24-hr stimulation. Unstimulated cells adherent to FN or VN had already released small amounts of IL-8, and both VN- and FN-adherent cells produced, almost invariably, a higher level of cytokines than BSA-exposed cells after additional stimulation. These results show that mast cell adhesion to matrix proteins by itself has only selected and minor effects, but additional activation of mast cells by secretory stimuli causes significantly enhanced cytokine gene expression and secretion, suggesting that mast cells are far more active in their natural tissue environment than hitherto suggested from data in suspension cultures.

Previous studies have suggested that transforming growth factor-beta 1 (TGF-beta1) acts as an autocrine growth inhibitor on normal human melanocytes, while melanoma cells may not respond to this stimulus. The role of other TGF-beta isoforms such as TGF-beta2 and TGF-beta3 remained less well characterized. In the present study, the mRNA and protein levels of all three isoforms of TGF-beta were analyzed in a panel of human melanoma cell lines and in cultures of normal human melanocytes in vitro. Northern analysis showed that the degree of TGF-beta1, -beta2, -beta3 mRNA expression varied considerably in melanoma cells, whereas TGF-beta expression was very low in melanocytes. In melanoma cells, secreted amounts of TGF-beta1 and TGF-beta3 were found increased in comparison to normal melanocytes: 615 pg/ml vs. 118 pg/ml and 193 pg/ml vs. 30 pg/ml (mean values). In addition, low levels of TGF-beta2 were detected (mean value: 28 pg/ml). Although TGF-beta secretion increased, the proliferation of melanoma cells was found to be only moderately inhibited by TGF-beta isoforms, in contrast to its strong antiproliferative effect on normal human melanocytes: - 15%, -11%, and -18% vs. -52%, -46%, and -50% average inhibition at 0.5 ng/ml TGF-beta1, -beta2, and -beta3, respectively. The different efficacy of TGF-beta on melanocyte and melanoma cells was highly significant (P0.0001); in addition, TGF-beta-dependent growth inhibition of melanoma cells from primary tumors vs. cells from metastases showed a trend for further decreased response for the metastatic populations (Por = 0.075). Measurements of DNA synthesis revealed even more pronounced differences between melanocytes (-86%, -78%, and -80% inhibition, respectively, for TGF-beta1, -beta2, and -beta3) and melanoma cells (no inhibition). Our data show loss of responsiveness of melanoma cells to the growth-inhibitory function of TGF-beta isoforms but not of melanocytes. Although melanoma cells are not growth-inhibited by all three TGF-beta isoforms, they secrete significantly higher levels of TGF-beta, as compared to melanocytes. The reduced response indicates their escape from TGF-beta surveillance with ongoing tumor progression.

Scleromyxoedema, a disseminated papular and sclerotic variant of lichen myxoedematosus, is a rare disease with a chronic progressive course, and little tendency towards spontaneous remission. The treatment of scleromyxoedema has been largely ineffective. Aggressive chemotherapeutic agents have been used, often leading to therapy-related morbidity and mortality. We report a 41-year-old woman with scleromyxoedema, associated with a monoclonal gammopathy of IgG-kappa type, whose condition almost completely cleared with 12 monthly sessions of extracorporeal photopheresis. The patient had previously not responded to isotretinoin, and chlorambucil with prednisolone.

Experimental animal models have shown that various cytokines, depending of their specific properties, may support growth and metastasis of tumor cells or even lead to tumor rejection. The analysis of expression of cytokine genes by melanoma cell lines indicated that melanoma cells constitutively produce both autostimulatory and inhibitory cytokines. Using reverse transcriptase polymerase chain reaction analysis, simultaneous expression of several cytokines, including interleukin-1 beta (IL-1 beta), IL-6, IL-8, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor, by melanoma cells was found. The same cytokine transcripts were detected in melanocytes, suggesting that cells of the melanocytic lineage express a specific pattern of cytokines in vitro. All these cytokines are known to be able to stimulate effector cells of the host. Additionally, production of mRNA for IL-10, a cytokine with potential immunosuppressive properties, was detected in melanoma cells and melanocytes. These and other cytokines are likely to be involved in the immune response to cancer and at this time it is unknown what the net effects of multiple cytokines are on the outcome of the host response to tumor.

Aberrant proliferation of tumor cells characterizes cancer growth. Investigations of cellular growth control mechanisms have contributed to our understanding of carcinogenesis and to the identification of compounds with specific antitumor activity. Many cytokines have been found to act on melanoma tumors, either produced by the tumor cells themselves or by infiltrating host cells. Purified cytokines allowed direct comparison of the growth response between normal human melanocytes and malignant melanoma cells. The present paper summarizes results of a series of our own experiments not yet published and data from a review of the recent literature. Proliferation of normal human melanocytes is enhanced by several cytokines, including basic fibroblast growth factor (bFGF), melanoma growth stimulatory activity (MGSA), hepatocyte growth factor (HGF), and mast cell growth factor (MGF). Melanoma cells are additionally stimulated by epidermal growth factor (EGF)/transforming growth factor alpha (TGF-alpha) and nerve growth factor (NGF). Tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta 1 (TGF-beta 1), and interleukin (IL)-6 are all potent inhibitors of melanocyte growth, but they are less effective on melanoma cells or even stimulate their growth. Interferon (IFN)-alpha and IFN-gamma inhibited proliferation of melanoma cells but not of melanocytes, whereas IFN-beta showed antiproliferative effects in both cell types. These findings suggest an alteration in growth control mechanisms during melanocyte transformation and possibly play a role in melanoma pathogenesis.

In order to enable a direct comparison of gene expression in human melanoma cells and in normal human melanocytes, culture conditions were investigated under which both cell populations can be grown in vitro. Five of 13 melanoma cell lines tested could be cultured to confluence in a melanocyte medium containing fetal calf serum, 12-O-tetradecanoylphorbol-13-acetate and stimulators of cyclic adenosine monophosphate, whereas none could be grown to confluence in a serum-free hormone-supplemented melanocyte medium containing basic fibroblast growth factor and other mitogens. In both melanocyte media the melanoma cells showed signs of increased morphological differentiation with dendrite formation. Normal human melanocytes could be grown in melanoma cell medium for a few days, after which the cultured cells showed a less differentiated phenotype. Since morphological changes may reflect variations in gene expression, we suggest that comparative studies on gene expression of benign and malignant melanocytes should also include thorough investigation under identical culture conditions.

Hailey-Hailey disease (HHD; OMIM 169600), also known as benign familial pemphigus, is a rare genodermatoses firstly described in 1939 by the Hailey brothers. HHD is characterized by impaired keratinocyte adhesion resulting in widespread intraepidermal acantholysis. Clinically, lesions appear as vesicles and bullae forming upon rupture, painful erosions, and rhagades in flexural areas. HHD is a chronic disease with a relapsing-remitting clinical course.   Exacerbations are mainly triggered by sweating, minor trauma, and secondary infections. No curative treatment is available. Patient management can be challenging. Mild cases can be controlled successfully with intermittent courses of topical corticosteroids and antibiotics., (Copyright © 2022, StatPearls Publishing LLC.)